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Ascentage Pharma Announces Updates on the Clinical Development of APG-2575, including an ORR of 70% in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia

On December 9, 2020 Ascentage Pharma (6855.HK), a globally focused, clinical-stage biotechnology company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, reported updates on the clinical development of the company’s novel Bcl-2 inhibitor APG-2575, further demonstrating the drug candidate’s therapeutic potential (Press release, Ascentage Pharma, DEC 9, 2020, View Source [SID1234572550]).

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APG-2575 is a novel, orally administered small-molecule Bcl-2‒selective inhibitor being developed by Ascentage Pharma. APG-2575 is designed to treat hematologic malignancies and solid tumors by selectively blocking antiapoptotic protein Bcl-2 to restore the normal apoptosis process in cancer cells. As a bona fide Bcl-2 inhibitor, APG-2575 demonstrated desired target engagement. APG-2575 selectively binds to Bcl-2, disrupts Bcl-2:BIM complexes, and releases the proapoptotic protein BIM. Freed BIM subsequently activates BAX/BAK for pore formation on the mitochondria membrane, leading to mitochondrial outer-membrane permeabilization (MOMP), cytochrome c release, caspase activation, and apoptosis of cancer cells. APG-2575 is the first China-developed Bcl-2 inhibitor having entered clinical development in China. As a single agent, APG-2575 has potent antitumor activity in Bcl-2-dependent tumor cells, and has shown a broad range of antitumor activities when combined with other oncologic drugs. Previously, APG-2575 had received clearances and approvals for multiple Phase Ib/II clinical studies in China, Australia, and the US, and is currently being developed in a range of hematologic malignancies globally.

Highlights of the update

In total, 9 clinical studies are ongoing globally, with over 100 patients who have been administered APG-2575 at doses ranging from 20 mg to 1200 mg for the treatment of chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), multiple myeloma (MM), acute myeloid leukemia (AML), and high leukocyte acute leukemia (HCL), etc.
Studies of APG-2575 in the treatment of relapsed/refractory CLL (r/r CLL) have enrolled over 30 patients. Preliminary results show that an objective response rate (ORR) of 70% has been reached in evaluable patients.
On safety:
Maximum tolerated dose (MTD) has not been reached, and no dose-limiting toxicity (DLT) was observed.
No clinical or laboratory tumor lysis syndrome (TLS) was observed.
Most treatment-related adverse events (TRAEs) were of Grade 1 or 2.
Limited cases of neutropenia and thrombocytopenia.
APG-2575 has been granted three Orphan Drug Designations (ODDs) by the US FDA, for the treatment of CLL, MM, and Waldenström macroglobulinemia (WM).
"APG-2575 is a key drug candidate of Ascentage Pharma’s apoptosis-targeted pipeline," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "As the first China-developed Bcl-2 inhibitor having entered clinical development in China, APG-2575 as a single agent or in combinations has demonstrated great therapeutic potential and clinical advantages. We are accelerating the global clinical development of this drug candidate, which we hope will soon translate into a new therapeutic option for patients in China and around the world."

Stellar Results from Kintor’s GT90001 and Opdivo Combo Therapy in the Second-line Treatment of Advanced Liver Cancer: ORR Reached up to 40%

On December 9, 2020 Kintor Pharmaceutical Limited (HKEx: 9939) reported that the Group has collected positive data in phase II clinical trials of combination therapy of ALK-1 (GT90001) antibody and PD-1 (Nivolumab or Opdivo) antibody for the second line therapy of advanced hepatocellular carcinoma ("HCC") in Taiwan (the "Phase II Clinical Trial") (Press release, Suzhou Kintor Pharmaceuticals, DEC 9, 2020, View Source [SID1234572549]). The preliminary data of the ongoing Phase II Clinical Trial showed positive efficacy and safety results. The data collected in the Phase II Clinical Trial will be released at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium (ASCO-GI) to be held between January 15-17, 2021.

Poster presentation
Abstract Title:
Safety and efficacy of combination of GT90001, an anti-activin receptor-like kinase-1 (ALK-1) antibody, and nivolumab in patients with metastatic hepatocellular carcinoma (HCC)
Abstract Number: 326
First Author: Chiun Hsu, MD

GT90001 is a fully humanised monoclonal antibody that inhibits ALK-1/TGF-β signal transduction and tumor angiogenesis and a potential first-in-class antibody for which we obtained an exclusive global license from Pfizer, Inc. in February 2018. The Phase II Clinical Trial was commenced on May 7, 2019 in Taiwan to evaluate the safety and efficacy of GT90001 in combination therapy with Nivolumab in patients with advanced HCC who were progressed on or intolerant to first line therapy with Sorafenib or Lenvatinib.

The Phase II Clinical Trial (NCT03893695) was a single-arm, open-ended and two-stage clinical trial. The Phase II Clinical Trial mainly observed the safety, tolerability and anti-tumor activity of the combination therapy of GT90001 and Nivolumab. In the first stage (safety evaluation cohort), six patients were enrolled in the dose group of 7mg/kg of GT90001 biweekly and 3mg/kg of Nivolumab biweekly. In the second stage (expanded cohort), 14 patients were enrolled at the same dose for combination therapy. According to Response Evaluation Criteria in Solid Tumours (RECIST) v1.1, patients received treatment until experiencing disease progression or intolerable toxicity was developed. The primary efficacy endpoint was the objective response rate (ORR) assessed by the investigators.

From July 9, 2019 to September 30, 2020, among the 20 evaluable patients, eight patients (40.0%) were observed partial remission (PR). The side effects were well tolerated and manageable. The pharmacokinetic parameters of GT90001 and Nivolumab are similar to those of monotherapy.

Dr. Tong Youzhi, the founder, Chairman and CEO of Kintor Pharmaceutical, said, "Upon obtaining the exclusive global rights of GT90001, Kintor has implemented the development strategy to combine GT90001 with immunotherapy. GT90001, in combination with Nivolumab, has showed positive efficacy and safety results. We are actively initiating MRCT phase II/III clinical trials in China and US for the treatment of advanced HCC. Meanwhile, we are exploring innovative therapies for the treatment of other solid tumors."

About GT90001

GT90001 is a fully human monoclonal antibody against ALK-1 (Activin Receptor-Like Kinase-1, Activin Receptor-Like Kinase-1). Kintor Pharmaceutical obtained the global exclusive development, production and commercialization rights from Pfizer in 2018. ALK-1 antibody can inhibit tumor blood vessel growth, reduce blood flow and angiogenesis by blocking the ALK-1 receptor pathway, thereby slowing tumor growth and changing the tumor microenvironment. As a potential first-in-class innovative drug in the world, it is expected to be used in the treatment of various solid tumors.Pfizer has conducted two phase I clinical trials on GT90001 in the United States, Italy, South Korea and Japan, which showed good safety and preliminary effectiveness in more than 100 patients with advanced solid tumors. Currently, Kintor Pharmaceutical is conducting phase II clinical trial of GT90001 combined with Nivolumab (PD-1 antibody) for the treatment of advanced liver cancer in Taiwan.

Oblato Announces Discussion Outcome with FDA for Development of OKN-007 for Diffuse Intrinsic Pontine Glioma

On December 9, 2020 Oblato, Inc. (the Company), a wholly owned U.S. subsidiary of the Korean biotech company GtreeBNT Co., Ltd., reported it had official discussions with the FDA on a detailed plan for a phase 1/2 clinical trial to start developing a new treatment for Diffuse Intrinsic Pontine Glioma (DIPG), a rare pediatric disease, using its proprietary drug, OKN-007 (Press release, Oblato, DEC 9, 2020, View Source [SID1234572548]).

Through this FDA meeting, the Company obtained consent from the FDA on important matters, such as patient population, starting dose, approach for dose escalation, and criteria for evaluating disease response. Importantly, there was in depth discussion on how to actively utilize existing historical patient data instead of requiring a comparative group in consideration of the nature of DIPG, a severe rare pediatric glioma and the need for all patients to receive anti-cancer treatment. The FDA also gave detailed advice on pharmacokinetic assessment and standard of care radiation therapy during the clinical study. The detailed response from the FDA indicates their support and expectations for Oblato which is developing a new drug for the treatment of DIPG.

In particular, the FDA has been supportive of biopharmaceutical companies developing treatments for rare pediatric diseases. Furthermore, new drugs for rare pediatric diseases have been approved by the FDA if the efficacy was fully demonstrated even with a small clinical trial. In 2019, Vyondys 53 (golodirsen), a treatment for DMD (Duchenne muscular dystrophy) developed by Sarepta Therapeutics, was approved after just a single phase 1/2 clinical trial. Another example is Brineura (ceriponase alpha) that was developed by Biomarin and approved in 2017 for the treatment of CLN2/Batten disease after a single phase 1/2 clinical study.

"DIPG’s nonclinical studies using OKN-007 have been recognized as supportive to the proposed phase 1/2 trial plan for DIPG and were also fully accepted by the FDA during the meeting. If our treatment shows efficacy in the clinical study for DIPG, we will be able to apply for an NDA after the trial is completed," stated an official from the Company.

The FDA has already granted Oblato the Rare Pediatric Disease Designation for DIPG, and the FDA has officially indicated that Oblato would be eligible for a Rare Pediatric Disease Priority Review Voucher.

Rocket Pharmaceuticals Prices Upsized Public Offering of Common Stock

On December 9, 2020 Rocket Pharmaceuticals, Inc. (NASDAQ: RCKT) ("Rocket"), a clinical-stage company advancing an integrated and sustainable pipeline of genetic therapies for rare childhood disorders, reported the pricing of an upsized underwritten public offering of 4,642,858 shares of its common stock at a public offering price of $56.00 per share (Press release, Rocket Pharmaceuticals, DEC 9, 2020, View Source [SID1234572547]). The gross proceeds to Rocket from the offering are expected to be approximately $260 million, before deducting the underwriting discounts and commissions and other offering expenses. Rocket has granted the underwriters a 30-day option to purchase up to an additional 696,428 shares of its common stock.

All the shares in the offering are to be sold by Rocket. The offering is expected to close on or about December 14, 2020, subject to satisfaction of customary closing conditions. Rocket intends to use the net proceeds from this offering to further fund the development of its pipeline of gene therapies for rare diseases, including filing for marketing authorization for RP-L201 in the United States and Europe, accelerating the buildout of in-house manufacturing capabilities, and for general corporate purposes. J.P. Morgan, BofA Securities, SVB Leerink and Piper Sandler are acting as the joint bookrunning managers for the public offering.

The public offering is being made by Rocket pursuant to an effective shelf registration statement on Form S-3 that was previously filed with the U.S. Securities and Exchange Commission (the "SEC") and declared effective by the SEC. A final prospectus supplement relating to and describing the terms of this offering will be filed with the SEC. When available, copies of the final prospectus supplement and the accompanying prospectus relating to these securities may be obtained from J.P. Morgan Securities LLC, Attention: Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, from BofA Securities, NC1-004-03-43, 200 North College Street, 3rd floor, Charlotte, NC 28255-0001, Attn: Prospectus Department, or by email at [email protected], from SVB Leerink LLC, Attention: Syndicate Department, One Federal Street, 37th Floor, Boston, MA 02110, by telephone at (800) 808-7525, ext. 6132, or by email at [email protected], or from Piper Sandler & Co., 800 Nicollet Mall, J12S03, Minneapolis, MN 55402, Attention: Prospectus Department, by telephone at (800) 747-3924, or by email at [email protected]. You may also obtain these documents free of charge by visiting the SEC’s website at www.sec.gov.

This press release does not constitute an offer to sell or a solicitation of an offer to buy, nor shall there be any sale of these securities in any state or jurisdiction in which such an offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

NANOBIOTIX Announces the Filing of an Amended Registration Statement, Including an Estimated Initial Public Offering Range

On December 9, 2020 NANOBIOTIX (Paris:NANO) (Euronext: NANO – ISIN : FR0011341205 – the ‘‘Company’’), a clinical-stage nanomedicine company pioneering new approaches to the treatment of cancer, reported the filing of an amended registration on form F-1 in connection with its intention to issue and sell, subject to market and other conditions, 6,500,000 ordinary shares of the Company in an initial public offering of American Depositary Shares ("ADSs"), each representing the right to receive one ordinary share, in the United States (the "U.S. Offering") and a concurrent offering of ordinary shares in certain jurisdictions outside the United States to certain investors (the "European Offering" and together with the U.S. Offering, the "Global Offering") (Press release, Nanobiotix, DEC 9, 2020, View Source [SID1234572546]). The offering price per ADS is expected to be between $13.50 and $14.50, or between €11.15 and €11.97 per ordinary share (assuming an exchange rate of €1.00 = $1.2109, the exchange rate published by the European Central Bank on December 9, 2020).

Assuming an offering price of $14.00 per ADS in the U.S. Offering and €11.56 per ordinary share in the European Offering, which are the midpoints of the respective price ranges, the Company expects to receive net proceeds of approximately $79.6 million (€65.8 million) from the Global Offering. The Company intends to grant the underwriters a 30-day option to purchase, at the same price, additional ADSs and/or ordinary shares in an aggregate amount of up to 15% of the total number of ADSs and ordinary shares proposed to be sold in the Global Offering. If such option is exercised in full, the expected net proceeds to the Company will increase to approximately $92.3 million (€76.2 million).

All securities to be sold in the Global Offering will be offered by the Company. The ADSs have been approved for listing on the Nasdaq Global Select Market under the ticker symbol "NBTX." The Company’s ordinary shares are listed on the regulated market of Euronext Paris under the ticker symbol "NANO."

The Company plans to use the net proceeds of the Global Offering to advance the overall development of NBTXR3, prioritizing the treatment of locally advanced head and neck cancers, including approximately $58.1 million to advance its clinical trial of NBTXR3 in the United States and Europe for the treatment of locally advanced head and neck cancers through an interim analysis of efficacy data, and approximately $20.6 million to advance the development of its other clinical and pre-clinical programs. The Company expects to use the remainder of the net proceeds, if any, from the Global Offering for working capital funding and other general corporate purposes.

The Company expects that the net proceeds from the Global Offering, together with its cash and cash equivalents of €42.4 million as of September 30, 2020, will be sufficient to fund its operating expenses and capital expenditure requirements through the end of 2022.

Jefferies LLC is acting as global coordinator and joint book-running manager for the Global Offering, and Evercore Group, L.L.C. and UBS Securities LLC are acting as joint book-running managers for the U.S. Offering. Jefferies International Limited and Gilbert Dupont are acting as managers for the European Offering.

The final offering price per ADS in U.S. dollars and the corresponding offering price per ordinary share in euros, as well as the final number of ADSs and ordinary shares to be sold in the Global Offering, will be determined by the Company’s executive board following a bookbuilding process commencing immediately. The offering price per ADS and per ordinary share will be at least equal to the volume weighted average price of the Company’s ordinary shares on the regulated market of Euronext in Paris over the last three trading days preceding the start of the offering (i.e., December 7, 8 and 9, 2020), subject to a maximum discount of 10%.

On an indicative basis, the completion of the Global Offering would result in a dilution of approximately 25% of the Company’s outstanding share capital on a non-diluted basis (excluding the exercise by the underwriters of the option to purchase additional ordinary shares) and approximately 28% of the Company’s outstanding share capital on a non-diluted basis (in the event that the underwriters exercise in full their option to purchase additional ordinary shares (including in the form of ADSs)).

The ADSs and/or ordinary shares will be issued through a capital increase without shareholders’ preferential subscription rights by way of a public offering excluding offerings referred to in Article L. 411-2 1° of the French Monetary and Financial Code (Code monétaire et financier) and under the provisions of Article L.225-136 of the French Commercial Code (Code de commerce) and pursuant to the 2nd and 7th resolutions of the Company’s extraordinary general shareholders’ meeting held on November 30, 2020. The European Offering will be open only to qualified investors as such term is defined in article 2(e) of the regulation (EU) 2017/1129 of the European Parliament and of the Council of June 14, 2017.

The Company plans to announce the result of the Global Offering as soon as practicable after pricing thereof in a subsequent press release.

The existing liquidity contract between the Company and Gilbert Dupont is suspended until the end of the stabilization period.

The securities referred to in this press release will be offered only by means of a prospectus. When available, copies of the preliminary prospectus relating to and describing the terms of the Global Offering may be obtained from Jefferies LLC, 520 Madison Avenue New York, NY 10022, or by telephone at 877-547-6340 or 877-821-7388, or by email at [email protected]; or from Evercore Group L.L.C., Attention: Equity Capital Markets, 55 East 52nd Street, 35th Floor, New York, New York 10055, or by telephone at 888-474-0200, or by email at [email protected]; or from UBS Securities LLC, Attention: Prospectus Department, 1285 Avenue of the Americas, New York, New York 10019, or by telephone at 888-827-7275, or by email at [email protected].

A registration statement on Form F-1 relating to the securities referred to herein has been filed with the U.S. Securities and Exchange Commission ("SEC") but has not yet become effective. These securities may not be sold, nor may offers to buy be accepted, prior to the time the registration statement becomes effective. The registration statement can be accessed by the public on the website of the SEC.